Someone finally checked the lamotrigine heart warning against real patients
A 367,000-person study found a real signal in bipolar disorder. The absolute size of it is about 1 in 900 per year.
Well-supported by good-quality research. how we score evidence
The FDA's 2021 warning about lamotrigine and heart rhythm rested on laboratory work and on reasoning about who was plausibly vulnerable. It did not rest on a study that counted what happened to people. In 2025 an NIH-funded group did that study.
Using a large health-insurance claims database, they compared adults starting lamotrigine against adults starting commonly prescribed alternatives, in three groups: bipolar disorder, partial seizures, and generalised tonic-clonic seizures. Everyone was free of arrhythmia for six months beforehand. In the bipolar group — 153,852 on lamotrigine against 213,593 on alternatives — ventricular tachycardia occurred in 0.79% over one year against 0.68%, a hazard ratio of 1.33 (95% CI 1.12 to 1.57).
Both numbers deserve to be read. A 33% relative increase sounds serious. The same finding stated as an absolute difference is 0.11 percentage points, which is roughly one additional case per 900 people per year. Neither framing is the honest one on its own.
Two cautions. The signal reached statistical significance only in the bipolar group; in both seizure groups the confidence intervals crossed 1, which is what you would expect either from a genuinely small effect in a smaller sample or from confounding. And this is claims data — people prescribed lamotrigine differ from people prescribed the alternatives in ways a database cannot fully adjust for.
Worth asking
Does my own heart history put me in the group the FDA warning was written about, and if it does, does this change anything about monitoring.
What it is FDA approved for
Read off the label. Trial duration and approval year are shown only where they were recorded — never inferred.
- Maintenance treatment of bipolar I disorder (to delay time to occurrence of mood episodes, after acute stabilization)
- Epilepsy, adjunctive therapy (partial-onset seizures, primary generalized tonic-clonic seizures, Lennox-Gastaut syndrome; ages 2+)
- Epilepsy, conversion to monotherapy for partial-onset seizures (ages 16+)
Source
Association of ventricular arrhythmias with lamotrigine: an observational cohort study — Radwanski P, et al. (2025)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1038/s41598-025-01321-7
DOI: 10.1038/s41598-025-01321-7
How this was scored
- Study design
- Cohort study
- Funding
- Independently funded
- Published in
- Reputable peer-reviewed journal
- Sample size
- 367,445
- Preregistered
- No
- Conflicts disclosed
- Yes
- Independent of proponent
- Yes
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published August 5, 2026. Last verified August 19, 2026.
Questions
How strong is the evidence behind this?
Resolv rates this source "strong evidence". Well-supported by good-quality research. It scores 76 out of 100 on our published rubric. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Association of ventricular arrhythmias with lamotrigine: an observational cohort study — Radwanski P, et al. (2025). Published in: Reputable peer-reviewed journal. DOI: 10.1038/s41598-025-01321-7. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Cohort study. Funding: Independently funded. The researchers were independent of whoever benefits from the result. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is lamotrigine (Lamictal) FDA approved?
Yes — FDA approved for Maintenance treatment of bipolar I disorder (to delay time to occurrence of mood episodes, after acute stabilization), Epilepsy, adjunctive therapy (partial-onset seizures, primary generalized tonic-clonic seizures, Lennox-Gastaut syndrome; ages 2+), Epilepsy, conversion to monotherapy for partial-onset seizures (ages 16+). Approval is for a specific indication, not for everything the drug is prescribed for.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.